14-3-3 proteins mediate an essential anti-apoptotic signal
14-3-3 proteins mediate an essential anti-apoptotic signal
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DOI：
10.1074/jbc.m105971200
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发表时间：
2001-11-30
影响因子：
4.8
通讯作者：
Fu, H
中科院分区：
文献类型：
--
作者：
Masters, SC;Fu, H
14-3-3蛋白是一个高度保守的真核生物调控分子家族，在细胞周期调控和细胞死亡调控等许多生物学过程中发挥重要作用。它们能够通过结合和调节许多信号蛋白的活性来实现这些作用。14-3-3抑制Bad和其他促凋亡蛋白的能力表明14-3-3可以支持细胞存活。为了在全局意义上研究这个问题，使用了14-3-3/配体相互作用的特异性抑制剂difopein。Difopein表达诱导细胞凋亡。使用存活和死亡信号传导途径的各种组分的研究与14-3-3/配体相互作用在从上游促存活激酶到核心凋亡机制的信号转导中的重要作用一致。由于这些激酶在肿瘤发生过程中经常被激活，因此检测了difopein对由抗肿瘤药物诱导的细胞死亡的影响。发现difopein增强顺铂杀死细胞的能力。这些数据支持14-3-3通过与Bad和其他配体结合对细胞存活信号传导至关重要的模型。14-3-3的抑制可以代表用于治疗癌症和涉及不适当的细胞存活的其它疾病的有用的治疗靶标。
The 14-3-3 proteins are a family of highly conserved eukaryotic regulatory molecules that play important roles in many biological processes including cell cycle control and regulation of cell death. They are able to carry out these effects through binding and modulating the activity of a host of signaling proteins. The ability of 14-3-3 to inhibit Bad and other proapoptotic proteins argues that 14-3-3 can support cell survival. To examine this issue in a global sense, a specific inhibitor of 14-3-3/ligand interactions, difopein, was used. Difopein expression led to induction of apoptosis. Studies using various components of survival and death signaling pathways were consistent with a vital role for 14-3-3/ligand interactions in signal transduction from upstream pro-survival kinases to the core apoptotic machinery. Because these kinases often become activated during oncogenesis, the effect of difopein on cell death induced by antineoplastic drugs was examined. It was found that difopein enhances the ability of cisplatin to kill cells. These data support the model that 14-3-3, through binding to Bad and other ligands, is critical for cell survival signaling. Inhibition of 14-3-3 may represent a useful therapeutic target for treatment of cancer and other diseases involving inappropriate cell survival.